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C Bertoni-Freddari

Publications and source records attributed to C Bertoni-Freddari.

At least 37 records · Page 2Linked to original sources

Morphological plasticity of synaptic mitochondria during aging.

A morphometric investigation has been carried out on the synaptic mitochondria of cerebellar glomeruli in young, adult and old rats by means of a computer-assisted image analysis technique. Mitochondrial volume density (Vv), numerical density (Nv), average volume (V) and average length (Skeleton = Sk) were investigated in tissue samples fixed, embedded and sectioned according to conventional electron microscopic methods. Vv was unchanged in the three groups of age taken into account. Nv was significantly increased in adult vs. young animals, whereas it was decreased in the old group as compared to both the other two groups investigated. V and Sk showed the same age-dependent changes: they significantly decreased in the adult vs. the young and the old groups of rats while increased significantly in the old rats vs. both the adult and young animals. A percentage distribution of Sk demonstrated that in the old group 20.6% of the population of synaptic mitochondria accounts for elongated organelles (> 5 microns) as compared to 8.6% and 5.3% in young and adult animals, respectively. The present findings match the changes previously reported by us on the ultrastructure of synaptic contact zones both in rats and human beings, and support the idea of an age-dependent dynamic adaptation in the morphology of synaptic mitochondria to cope with the metabolic needs of the pattern of synaptic connectivity they subserve.

Aging

Ultrastructure of phosphotungstic acid (PTA) positive deposits in the hippocampus of senile demented patients.

To perform a quantitative investigation on synaptic ultrastructural features in the human hippocampus in normal old and senile demented patients we stained our tissue samples by means of the ethanol-phosphotungstic acid (E-PTA) preferential technique. In addition to the synaptic contact zones, we found that structures similar to neurofibrillary tangles (NFT) and senile plaques (SP) were remarkably positive to our staining procedure, while the background was faintly electron lucent. On the basis of the E-PTA staining properties and specificity, we support that the reactive sites of these positive structures are represented by basic amino acids. The recently demonstrated presence of 4 basic amino acids (1 arginine, 3 histidine) in the cleaved fragment of the amyloid precursor protein (APP) suggest us to hypothesise that this APP portion may represent the common constitutive element of the many morphologically different alterations found in the brains of senile demented patients.

Aged

Compensatory enlargement of synaptic size in aging and senile dementia.

Synaptic contact zones in the dentate gyrus supragranular layer and cerebellar glomeruli of autoptic samples from adult, old and demented patients have been investigated by means of computer-assisted morphometric techniques. In physiological aging and senile dementia, the synaptic average area was significantly increased as compared with adult values in both the CNS areas investigated. Conversely, the number of contacts and their total surface contact area per unit volume of tissue were decreased. In animal models, the enlarged contact zones are reported to undergo perforations and splitting to modify synaptic connectivity. As against these assumptions, the increased synaptic size observed in our study appears to represent a compensative reaction of old and demented CNS to counteract the decrease in number and total contact area of the synaptic junctions.

Aged

Enlargement of synaptic size as a compensative reaction in aging and dementia.

A quantitative investigation has been carried out on synaptic contact zones of dentate gyrus supragranular layer and cerebellar glomeruli in autoptic samples from adult, old and demented patients. During physiological aging and senile dementia, the synaptic average area was significantly increased as compared to adult values in both the CNS areas investigated. Conversely, the number of contacts and their total surface contact area per unit volume of tissue were decreased. Current literature reports that, in animal models, enlarged synapses undergo perforations and splitting to modify synaptic connectivity. As against these assumptions, the increased synaptic size observed in our study appears to represent a compensative reaction of old and demented CNS to counteract the reduction in number and in total contact area of the synaptic junctions.

Aged

Morphological adaptive response of the synaptic junctional zones in the human dentate gyrus during aging and Alzheimer's disease.

A computer-assisted morphometric study has been carried out on ethanol phosphotungstic acid (E-PTA) stained synaptic junctions in the human dentate gyrus supragranular layer from adult, old and Alzheimer's disease (AD)-affected patients. The number of synapses per unit volume of tissue (Nv = numerical density), the average area of the single junction (S) and the total area of the synaptic contact zones in a unit volume of tissue (Sv = surface density) were the 3 parameters taken into account. The synapse to neurone ratio was also calculated for each patient. During physiological aging, Nv and Sv significantly decreased and S increased, respectively. In the AD hippocampi, Nv and Sv underwent a further decrease which was in the range of more than 40% with reference to the adult values. S was the same as the old control group. In comparison with the adult values, the number of synapse/neurone decreased by 15.6 and 48% in old and AD patients, respectively. Nv, S and Sv, while reporting on discrete ultrastructural features of the synaptic junctional zones, are closely related to each other and, taken together per group of patients, may represent a reliable index of the morphological adaptive changes taking place at the synapses. Thus, the significant increase of S both in old and AD hippocampi may be regarded as a CNS plastic response to aging and disease, although the marked decrease of Nv and Sv supports that in AD synaptic ultrastructural alterations proceed beyond a critical threshold for functional recovery.

Aged

Computer-assisted morphometry of synaptic plasticity during aging and dementia.

A computer assisted morphometric study has been carried out on synaptic membranes in the dentate gyrus supragranular layer and cerebellar glomerulus from adult, old and demented patients. Numerical (Nv) and surface (Sv) densities as well as average area (S) of the synaptic contact zones were calculated directly on electron microscopic negatives by means of an ASBA (Wild Leitz, AG) image analyzer properly programmed. The results showed a decrease of Nv in both the CNS areas investigated during aging and, to a higher extent, in senile dementia. S was found to be significantly increased in old and demented CNS as compared with adult values. In the old hippocampus Sv was decreased by 40% whereas no significant difference was present between old and adult cerebellum; in senile dementia this parameter underwent a significant decrease in both areas investigated. We interpret the present findings in terms of morphological remodelling capability of the synaptic junctional zones during aging and disease.

Aged

Quantitative morphology of the zinc-iodide-osmium (ZIO) stained synaptic vesicles.

A computer assisted morphometric method has been elaborated to quantify synaptic vesicles evidenced by means of the Zinc-Iodide-Osmium (ZIO) staining procedure in nerve endings of a very discrete area of the cerebellar granular layer: the glomerulus. The following parameters were calculated directly on electron microscopic negatives of 4.67 microns 2 of surface terminal area: number of vesicles per unit area (Na), and per unit volume (Nv), volume density (Vv), average diameter (d) and average volume of the single vesicle (V). Ultrastructural changes taking place at nerve endings also cover synaptic vesicles, thus quantitative studies regarding vesicle population at synaptic regions can be correlated to functional changes occurring in the process of chemical transmission and reflect the plasticity of synaptic junctional zones. Although this histochemical staining method generally is referred to as unspecific, after comparing our data with the available literature reports, we propose that ZIO-positive vesicles could have a physiological significance. These ZIO-positive organelles could take part in the intraterminal homeostatic control of Ca++ ions.

Animals

Age-dependent deterioration of neuronal membranes and the pathogenesis of Alzheimer's disease: a hypothesis.

Senile dementia of the Alzheimer's type (SDAT) is considered either a specific pathological condition unrelated to normal aging or an accumulation of brain aging alterations leading to clinical dysfunction. In the present paper a hypothesis is formulated to reconcile these two issues to a common denominator, i.e. the increased age-dependent deterioration of the neuronal membrane. If this holds true, normal aging and SDAT may be considered as two different aspects of the same problem and specific interventions to slow down the former can delay the onset of the latter to older ages.

Aging

Quantitative morphology of synaptic plasticity in the aging brain.

Quantitation of synaptic ultrastructural changes is of great importance in neurobiology, since merely qualitative alterations, if not extreme, are not readily detectable. In the present paper we discuss our previous and present findings on the number (numerical density: Nv), size (average length of the synaptic profiles: L) and surface contact area (surface density: Sv) of the synaptic junctions in aging rodent and human brains. We found that number and size of the synapses are in a close inverse relationship so as to maintain the total surface contact are among the nerve cells constant. These three parameters are closely related to each other, their quantitation may thus represent a reliable index of the morphological aspects of synaptic plasticity, i.e. the modification of ultrastructure occurring at synaptic membranes after transient changes in synaptic activity. During aging, the morphological plasticity of synapses appears to be seriously impaired: the number of synapses and the total surface contact area among the nerve cells are markedly reduced. However, old nerve cells seem to retain the ability to modify their synaptic endings and to partially compensate for the reduced surface density of the contact zones by expanding the average size of the persisting junctions. Our recent studies on synaptic plasticity in human brains from old and demented subjects showed that while the size of the synaptic contacts remains constant, the numerical and surface densities undergo a further decrease in demented brains relative to that in normal aging.

Adult

The effect of chronic hydergine treatment on the plasticity of synaptic junctions in the dentate gyrus of aged rats.

The number of synapses (Nv), the surface density of contact zones (Sv) as well as the average size (S) of E-PTA stained synapses in the supragranular layer of the dentate gyrus from adult (12 months), old (30 month), and Hydergine-treated old (30 months) rats were measured by using quantitative morphometric techniques. In old animals, Nv and Sv were significantly reduced, whereas S was significantly increased as compared with the values in adult rats. Hydergine (Codergocrine mesylate) treatment of old animals (3 mg/Kg/day for 4 weeks) influenced these three parameters, differentially. The Sv in aged animals receiving Hydergine, relative to that in untreated old rats, was significantly increased; the number and size of synapses in the treated old rats were significantly higher and smaller, respectively, than that in old controls. We interpret the present findings to indicate a modulating effect of Hydergine on the morphological plasticity of synaptic junctions in the dentate gyrus of aged rats.

Aging

Quantitative investigation of the morphological plasticity of synaptic junctions in rat dentate gyrus during aging.

The morphological plasticity of synaptic junctions was investigated by means of quantitative stereology in the dentate gyrus supragranular layer of young (3 months), adult (12 months) and old (30 months) female Fisher 344 rats. The numerical (Nv) and surface (Sv) density and the average surface area (S) of EPTA-stained synaptic junctions were calculated on 100 EM pictures per age group. We found that Nv significantly increased between the young and adult group and decreased in old animals when compared both to 3 and 12 months of age. Sv was unchanged in young and adult rats, whereas it underwent a significant reduction in the old group. The percentage distribution of S showed that at 3 months of age the majority of the synaptic population had an average size ranging between 0.12 and 0.20 micron 2, whereas during adulthood and aging there was a shift towards smaller and larger synaptic contacts, respectively. Taking into account Nv, Sv and S all together per age group, the present findings demonstrate that the morphological aspect of synaptic plasticity is markedly influenced by time and that during aging it undergoes a serious impairment. The possible involvement in memory and learning processes of these synaptic age-related morphological adaptations and the fact that the investigated junctions are supposed to be cholinergic is discussed.

Aging

Vitamin E deficiency alters the in vivo Rb+ discrimination of rat brain cortical cells.

The in vivo Rb+ uptake and release of rat brain cortical cells of 11-months-old rats fed with a vitamin E deficient diet was investigated. The animals were treated with a daily dose of 30 mg RbCl/100 g body weight for 14 days. After discontinuation of the RbCl treatment the animals were killed at intervals of 2, 4, 9 and 15 days, respectively. The intracellular Rb+ and K+ contents were analyzed by energy dispersive X-ray microanalysis, whereas concentrations of these two ions were determined by atomic absorbtion spectrophotometry in the serum and cerebrospinal fluid. Vitamin E deficient rats accumulate more Rb+ than age-matched normally fed animals at any time taken into account. Rb+-discrimination ratios calculated on the basis of Rb+ and K+ contents of both, cortical cell cytoplasm and cerebrospinal fluid, are higher in vitamin E deficient rats than in the controls (+20%), which supports the view that the enhanced membrane lipid peroxidation induced by vitamin E deficiency impairs the passive membrane permeability for Rb+ (and K+).

Aging

Age-related morphological rearrangements of synaptic junctions in the rat cerebellum and hippocampus.

A quantitative investigation has been carried out on the age-related morphological changes of the synaptic junctions in the cerebellar glomeruli and in the supragranular layer of the hippocampal dentate gyrus of young (3 months), adult (12 months) and old (28-30 months) rats. The numerical (Nv) and surface (Sv) density as well as the average length (L) of E-PTA stained synapses was calculated by means of morphometric methods. The results we obtained showed a similar trend in both these areas of the CNS. Nv significantly increased between young and adult rats and significantly decreased in the old group, when compared both to young and adult animals. Sv appeared to be unchanged comparing young and adult animals, whereas it was significantly reduced in the old group. L showed a decrease between 3 and 12 months of age and appeared to be markedly increased in the old animals when compared to adult values. From the present findings it can be inferred that number (Nv) and size (L) of the synapses are in a close inverse relationship which, through the organism's life span, aims to maintain the constancy of the surface contact area (Sv) among the dendritic network. By considering Nv, L and Sv altogether per age group, we were able to obtain a reliable measurement of the morphological aspect of synaptic plasticity through different periods of the life. With regard to aging we found that, despite the 'compensative synaptogenesis' brought about by the increased size (L) of the synaptic appositions, the reactive capacity of old nerve cells is seriously impaired.

Age Factors

Amiloride inhibits the PHA-evoked mouse splenic lymphocyte proliferation.

The present study was aimed to ascertain whether Na+ influx can be involved in regulation of blastogenesis and proliferation of PHA stimulated mouse splenic lymphocytes. The cells were cultivated in the presence of different concentrations of amiloride, an inhibitor of passive Na+ influx, and cellular activation was monitored by 3H-thymidine incorporation and blast index determination. The drug was not toxic and inhibited cell growth in concentrations ranging from 1 X 10(-3) to 1 X 10(-5) mmol/ml. The results are in agreement with the hypothesis that Na influx is necessary for PHA evoked mouse splenic lymphocyte activation.

Amiloride

Chronic dietary choline modulates synaptic plasticity in the cerebellar glomeruli of aging mice.

A morphometric investigation was carried out on ethanolic phosphotungstic acid (E-PTA) stained synaptic junctions in the cerebellar glomeruli of adult, old, old choline-deficient and old choline-supplemented mice. Numerical (Nv) and surface (Sv) density as well as average length (L) of the synapses were calculated on 100 pictures per group. A significant reduction of Nv and Sv, as well as an increase of L was found during aging. Choline deficient animals did not show any change as compared to old animals of the same age. In choline supplemented mice Nv and Sv were significantly increased and L significantly decreased, respectively, as compared to old control littermates. No difference was found between adult and choline supplemented mice. In the cerebellar glomeruli only a small fraction of fibers are cholinergic, therefore the present findings support the idea that dietary choline can influence systems other than cholinergic. The possible role of choline supplementation in the modulation of synaptic plasticity via the synthesis and/or turnover of neuronal membrane choline phospholipids, is discussed.

Animals

A modulating effect of Hygergine on the synaptic plasticity of old rats.

The morphological plasticity of E-PTA stained synaptic junctions was investigated by means of quantitative morphometry in the dentate gyrus supra-granular layer of adult, old and old-Hydergine treated rats. Numerical (Nv) and surface (Sv) density as well as average size of the synapses (S) were the three parameters considered. During aging, Nv and Sv significantly decrease whereas S increases. Hydergine treatment to old rats resulted in a significant increase of Nv and Sv and a significant decrease of S. Present findings are interpreted as a modulating effect of Hydergine on the synaptic plasticity of old rats.

Aging